Monoallelic deletion in the 5′ region of the thyroglobulin gene as a cause of sporadic nonendemic simple goiter

The cause of sporadic simple goiter is unknown in most cases. Family studies have suggested that this disorder may have a genetic component in some patients. We have previously demonstrated that some cases of endemic and nonendemic simple goiter are associated with a mutation within exon 10 of the thyroglobulin gene. Here we report a study of 50 cases diagnosed as having nonendemic simple goiter, and found 1 case with a large heterozygous deletion within the thyroglobulin gene. The deletion involves the promoter region and the 11 first exons of this gene and is associated with a euthyroid state. We hypothesize that the absence of thyroglobulin synthesis from the deleted allele may be responsible for a decreased level of thyroglobulin mRNA. Euthyroidism would be achieved by thyrotropin (TSH) stimulation but at the expense of goiter development.